EP2407132B1 - Device for preparing an eye for introducing a photostabilizer - Google Patents

Description

The invention relates to a device for preparing an eye for the introduction of photosensitizer in ocular tissue with a source of laser radiation, means for guiding and focusing the laser radiation with respect to the ocular tissue and with a computer for controlling said means. The invention also relates to a corresponding method for preparing an eye for the introduction of photosensitizer using laser radiation.

In ophthalmology it has been known for more than 10 years to change the biomechanical and biochemical properties of ocular tissue, in particular of the cornea, for therapeutic purposes by means of a so-called photosensitizer and electromagnetic radiation.

The human eyeball is bounded by the outer eye skin. Due to the intraocular pressure, the collagen-containing outer eye skin is stretched and gives the healthy eyeball an approximately spherical shape. In the posterior part of the eyeball, the outer eye skin consists of the white dermis (sclera). In the front area is the visible light permeable cornea (cornea).

Deformations of the outer eye skin can be the cause of ametropia. For example, a form of myopia, the axis myopia, may be the result of scleral longitudinal growth of the eyeball. An ellipsoidal surface of the cornea may result in a form of astigmatism, also known as astigmatism. Another disease of the cornea is called keratoconus. In keratoconus, due to morbid softening of the cornea, there is a progressive thinning and conical deformation of the cornea of the eye. As the bulge increases, the cornea below the center becomes thinner. It can break through and scar. This permanently reduces the visual acuity. The causes of keratoconus are still largely unknown today. He occurs familial heaped up, which among other things suggests a genetic disposition. Another risk factor for the development of keratoconus is atopy, such as allergic diseases.

The conventional therapy of advanced keratoconus is to remove the diseased cornea and replace it with an allograft. However, such an operation is an organ transplantation with the associated risks and complications. Adequate vision is often achieved approximately two years after surgery. In addition, corneal transplantation in keratoconus mostly affects young people, which is why the transplant must work flawlessly for decades.

An improved therapy of keratoconus stabilizes the cornea by cross-linking. The treatment allows photochemical, non-tissue-removing stabilization or alteration of the biomechanical and biochemical properties of the cornea. The treatment principle is also applicable to other affected regions of the eye. A photosensitizer solution is introduced into the eye tissue to be altered and exposed to primary radiation. The primary radiation used is electromagnetic radiation in the wavelength range from about 300 nm to 800 nm (UV-A radiation or visible light).

Corresponding devices for the treatment of the outer eye skin are known from the documents WO 2007/128581 A2 and WO 2008/000478 A1 known.

The EP 1 561 440 B1 describes a device in which a homogeneous distribution of the radiation in the ocular tissue is produced with a relatively complex structure. A shaped body is placed there on the cornea to bring it into a desired shape while using electromagnetic radiation and the photosensitizer the ocular tissue is changed in terms of its strength. Such a shaped body can also be used in connection with the present invention.

A device according to WO 2007/128581 A2 serves to solidify the sclera located in the posterior part of the eye. The primary radiation can act on the sclera through the interior of the eye or by lying on the outside pillows. A photoinitiator or photosensitizer causes cross-linking in the sclera. This counteracts scleral growth and prevents progression of axonal myopia.

The EP 1 854 438 A1 describes an ophthalmic device for the prevention of myopia, in which the sclera is solidified by means of a photosensitizer.

The publication WO 2008/000478 A1 describes an irradiation system for biomechanical stabilization of the cornea. Here too, crosslinking at the cornea can be effected in conjunction with a photosensitizer. The radiation system offers the possibility to treat specific diseases, such as keratoconus.

The US 2009/187171 A1 describes producing cuts in volumes within the stroma, with the volumes completely in the stroma. This is to change the shape of the cornea due to the intraocular pressure.

The change in shape and / or mechanical properties of ocular tissue, especially the cornea and generally the sclera by means of an incorporated photosensitizer and electromagnetic radiation is well known as such in the art, especially as mentioned above. With regard to the chemical composition of the photosensitizer, reference is made to the prior art, also with regard to the type of electromagnetic radiation used, in particular the suitable wavelengths associated with certain photosensitizers.

However, a routine use of the crosslinking therapy on the ocular tissue is precluded by complex dependencies. The relationships between the doses used and their effect in eye tissue are very diverse. As a dose in this sense, in particular, the electromagnetic radiation in terms of their intensity and their distribution in space and time; the photosensitizer used in terms of its chemical structure, concentration, and exposure in space and time. The effects of different doses of these parameters on and in the ocular tissue of a patient are very dependent on characteristics (measurement data) relating to the patient. It should be noted in particular that the effect of the crosslinking carried out with the radiation and the photosensitizer may also be undesirable up to damage to the eye tissue or the function of the eye.

Currently, riboflavin has proven to be advantageous as a photosensitizer. In order to introduce riboflavin into the cornea, in the prior art, the corneal epithelium must be at least partially removed because it hinders the penetration of riboflavin into the cornea, so to speak represents a barrier to the diffusion of riboflavin molecules into the corneal tissue. However, the removal is The epithelium usually associated with pain for the patient and also the subsequent healing process is not always without complications.

The invention has for its object to provide a device of the type mentioned, which allows a gentle introduction of the photosensitizer in the eye tissue, especially in terms of depth. In particular, the cross-linking in ocular tissue should also be controllable in a simple manner.

For this purpose, the invention provides a device according to claim 1 for preparing an eye for the introduction of photosensitizer in ocular tissue.

This makes it possible to introduce the photosensitizer in one or more channels in a simple manner, without the need for this significant parts of the epithelium must be removed or unfolded.

The laser radiation used to create the channel or channels can be generated by means known as such. Are known for generating the channels required sources of laser radiation, for example, from the so-called femto-LASIK. There laser radiation is used, for example, a femtosecond laser as a so-called "laser scalpel" to cut eye tissue by "evaporation" (cavitation bubbles) with the energy of the laser light. In femto-LASIK, the so-called flap cut is produced with the laser scalpel, ie a lid is cut out of the epithelium from the side and folded away. For example, an excimer laser in the exposed stroma to ablate the cornea to perform an ablation. Pulsed lasers with pulse lengths in the picosecond range and in the nanosecond range are also suitable for generating the channels.

The term "channel" in the sense of the present invention does not mean a cut surface for producing a so-called flap, as it is known in femtosecond LASIK.

The means used for the present invention for guiding and focusing the laser radiation with respect to the eye tissue can be taken from this technique. According to the invention, however, the computer controlling the optical means for guiding and focusing the laser radiation is, according to the invention, programmed in such a way that the foci of the laser radiation successively follow one another Straight or curved line are moved so that so-called cavitation bubbles in the tissue, a channel or multiple channels arise, which extend from the surface of the eye tissue, ie in particular the cornea, in the interior of the eye tissue, so that a photosensitizer, which at the entrance of the Channel is brought into the canal and thus into the interior of the eye tissue can penetrate. In this case, the channels are preferably produced in such a way that the individual adjacent cavitation bubbles each have such a distance from each other ("spacing") that the structure and stability of the tissue is impaired as little as possible. On the other hand, the distance between the cavitation bubbles which produce the channel should also be so small that the photosensitizer introduced into the channel in the form of a solution, e.g. B. riboflavin, penetrates in the desired manner through the channel, so to speak, from Kavitationsblase to Kavitationsblase in the tissue. In the areas between adjacent cavitation bubbles, therefore, the penetration of the photosensitizer solution takes place by diffusion. Thus, for the purposes of this invention, the term "channel" is not necessarily to be understood as a continuous, completely tissue-free cavity, although on the other hand, completely continuous channels within the meaning of the invention are conceivable.

According to a variant of the invention, the channel can also follow a curved line, since by focusing the laser radiation in the interior of the tissue with focus points along the curved line, a channel shape deviating from the straight line can be generated. In all the mentioned channel shapes can be created by stringing the foci of the laser radiation with a sufficiently dense distance through them so-called "photodisruption" of the channel with the desired diameter and with the desired geometric course.

The invention also makes it possible to adjust the density of the channels in the eye tissue differently, depending on the location in the eye tissue, ie to set more channels at desired sites of the eye tissue than at other locations, which then has the consequence that where the canal density is greater is also the density of the photosensitizer in the tissue is higher and thus the biomechanical and biochemical effect at such sites is different than those in the eye tissue in which the channel density is lower.

The density of the photosensitizer ultimately acting in the eye tissue can also be controlled by varying the depth of the channels in the cornea in a location-dependent manner.

Also, the density of the photosensitizer to be introduced into the eye tissue can be controlled by making the cross section of the one or more channels more or less large.

The width of a channel is preferably in the range of 0.1 mm ² to 1.2 mm, with each subinterval therein also disclosed herein.

When referring to "channel", it always means singular or plural.

With the device according to the invention, therefore, a channel system can be created in the cornea, which allows access from the outside to the interior of the cornea. The photosensitizer solution can then be injected so that it spreads in the corneal stroma. For this purpose, the channel system, depending on the ophthalmological indication, have one or more channels, for example, with a desired homogeneous distribution of the photosensitizer, the density of the channels (ie the number of channels per unit area or per unit volume) is substantially homogeneous in the treated area the cornea. For example, four channels may be placed in the four corneal segments, corresponding to the four segments of corneal projection onto a plane. The channel system can also be generated stochastically.

Also, the cross-sections of the individual channels can be designed by appropriate control of the focuses of the laser radiation optionally, for example, circular, rectangular, square, or even oval or slit-shaped.

Preferably, the channels extend substantially transversely to the axis (A) of the eye. The term "transverse" here essentially means "radial". "Radial" means a direction outward from the apex of the cornea.

An embodiment of the invention provides that the channel (s) traverses substantially the entire radial surface of the cornea with a substantially uniform channel density. This means, in other words, that at least in a given area at a given depth the cornea photosensitizer is brought into the comatom by diffusion homogeneously (uniformly with the same density).

It is contemplated that the one or more channels are connected to more than one opening, said one

Opening in the surface of the eye tissue is sufficient so that photosensitizer without obstruction in the one or more channels can be introduced, for. B. with a fine syringe or the like.

The said openings, through which the channels are accessible from the outside, are preferably arranged at or near the edge of the cornea, ie at or near the limbus.

The generation of channels or cavities in the sense of the present invention is thus different from the generation of a so-called flap for the LASIK, d. H. the channels or cavities according to the invention do not cause the generation of a flap ("Deckelchens"), which can be folded to the side.

Another preferred embodiment of the invention provides that at least a part of the channels runs in a spiral shape.

In all described embodiments and embodiments of the invention, a gas, in particular air, can be injected into one or more channels or cavities.

Further preferred embodiments of the invention are described in the further dependent claims.

The invention will be explained in more detail with reference to the drawings.

• Fig. 1 schematisch eine Vorrichtung zum Präparieren eines Auges für das Einbringen eines Photosensibilisators in Augengewebe;
• Fig. 2 eine Hornhaut in Draufsicht mit einer schematischen Erläuterung der Erzeugung von Kanälen darin;
• Fig. 3 ein anderes Ausführungsbeispiel der Erfindung, bei der der Rechner so programmiert ist, dass er etwa kreissektorförmige Kanalgebilde im Augengewebe erzeugt zur Behandlung von insbesondere Astigmatismus;
• Fig. 4 einen axialen Schnitt durch eine Kornea mit Kanälen, die in unterschiedlichen Tiefen, bezogen auf die Oberfläche der Kornea, verlaufen; und
• Fig. 5 eine axiale Draufsicht auf eine Kornea, bei der zumindest ein Ring als Kanal geformt ist zur Behandlung von Hyperopie.

It shows:

• Fig. 1 schematically a device for preparing an eye for the introduction of a photosensitizer in ocular tissue;
• Fig. 2 a cornea in plan view with a schematic explanation of the generation of channels therein;
• Fig. 3 another embodiment of the invention, wherein the computer is programmed so that it generates approximately circular sector-shaped channel structures in the eye tissue for the treatment of particular astigmatism;
• Fig. 4 an axial section through a cornea with channels that extend at different depths with respect to the surface of the cornea; and
• Fig. 5 an axial plan view of a cornea, wherein at least one ring is formed as a channel for the treatment of hyperopia.

Fig. 1 schematically shows an eye 10 to be changed by introducing photosensitizer with regard to its biomechanical and / or biochemical properties. As such, this process is known as "corneal crosslinking." For example, the cross-linking, so-called cross-linking, enhances the mechanical stability of the cornea. The use of moldings can also change the shape of the cornea during channeling or cross-linking. In addition, the use of photosensitizers is also suitable for treating infectious inflammations of the cornea, with the resulting radicals killing invading germs.

An eye axis is designated by "A", this eye axis substantially coinciding with the optical axis of the means described below in more detail for guiding and focusing laser radiation.

The center (center) of the corneal surface (14a) is denoted by "M", so that a radial direction R can be defined therefrom.

Here, the eye tissue 12 to be cross-linked is substantially the cornea (cornea) 16 which is covered outwardly by the epithelium 14.

With the device to be described later, channels 18 are inserted into the cornea 16, the channels 18 being fluidly connected to ports 0 (ports), and the ports O allowing external access to the channels for entering photosensitizer solution , The channels 18 extend into the interior of the cornea 16 and terminate before the inner surface 16 a.

In the channels 18, a photosensitizer, for example riboflavin, is introduced, which penetrates into the channels and spreads therefrom by diffusion in the corneal tissue.

The device has a source 20 for laser radiation, for example a femtosecond laser as explained above, as for example for cutting a flap in the femto-LASIK is used. With regard to the means 24 for guiding and focusing the laser radiation 26 in the interior of the cornea 16, appropriate means known per se from femto-LASIK can also be used.

In contrast to LASIK, a computer 22, which controls the laser beam source 20 and the optical means 24 for guiding and focusing the laser radiation 26, is programmed with a program P which controls the laser radiation 26 in a special way for generating the channels 18. For this purpose, when generating said channels 18 according to Fig. 1 the laser radiation 26 is displaced parallel in the direction of the arrows 28. The representation according to Fig. 1 shows a section A containing the axis A through the eye. In Fig. 1 a channel 18 is shown which is substantially parallel to the surface 14a of the cornea. The channel is accessible via an opening O, which is located near the limbus 30, from the outside. For example, a fine syringe may be introduced into the opening O to inject a photosensitizer solution or a gas, such as air, into the channel 18.

Fig. 2 shows a plan view of a cornea 16 and a running inside the cornea 16 channel 18 which is in the illustrated embodiment is spiral with additional openings O, which are distributed in the circumferential direction C at intervals. The approximately spirally extending channels 18 are arranged in the illustrated embodiment in a surface which extends substantially parallel to the surface 14a of the eye. In a modification of this embodiment, the channels 18 may also be arranged in a plane which is perpendicular to the axis A. Again, a variation provides that the channels extend in a plane that extends parallel to the back surface 16a of the cornea 16. *** " The choice of location and course of the channels 18 may depend on the given medical indication and be chosen accordingly.

In the illustrated embodiment according to Fig. 2 For example, the channels are positioned such that, at least in the area they define, the photosensitizer diffuses there substantially homogeneously in the corneal tissue.

In a modification of the embodiments shown in the figures, channels may also be axial, i. parallel to the axis A, at least partially.

Channels may also extend radially.

Also, all the above courses and arrangements of the channels are optionally combinable.

By choosing the diameter and geometric arrangement of the channels, the distribution of photosensitizer in the cornea can be optionally controlled, depending on the medical indication.

The channels are formed by focused laser radiation, in particular by means of a femtosecond laser, by cavitation bubbles generated by the laser focusses. In this case, it is preferably provided that adjacent cavitation bubbles do not completely overlap so that tissue residues remain between individual cavitation bubbles, which on the one hand stabilize the overall tissue in the structure and on the other hand are sufficiently permeable to the diffusion of photosensitizer in the channels.

It is also possible, instead of elongated channels to produce differently shaped cavities through said cavitation bubbles, in particular flat cavities in which z. B. at regular shorter intervals tissue areas as "posts" remain between the top and bottom surfaces of the cavity or cavities.

Fig. 3 shows in axial plan view a cornea with a channel system 18 ', 18 ", which is shaped in the shape of a sector of a circle (as shown) for the treatment of astigmatism in the contour Fig. 3 be formed two circular sector-shaped channel systems 18 'and 18 ", each with a different sector angle α ₁ and α ₂ .

Fig. 4 shows channels 18a, 18b, 18c which extend at different depths relative to the surface 14a of the cornea. In the Fig. 4 The various three depths for the channels shown schematically may be used for all of the structures and arrangements of channels detailed herein FIGS. 1, 2 . 3 and 5 as well as other embodiments.

Fig. 5 shows an annular channel 18 "'in a schematic plan view with two openings O, which connect the channel 18"' with the surface of the cornea. In a modification of the embodiment according to Fig. 5 can also be provided a plurality of annular channels, which are connected fluid-conducting either with each other and / or each individually with the surface of the cornea.

10

Auge

M

Mittelpunkt (von 10)

A

Augenachse

P

Programm

C

Umfangsrichtung

O

Öffnung

12

Augengewebe

14

Epithel, 14a Oberfläche (von 14)

16

Kornea, 16a Rückfläche (von 16)

18

Kanal

20

Quelle für Laserstrahlung

22

Rechner

24

Mittel

26

Laserstrahlung

28

Pfeile

30

Limbus

The invention also includes a method for preparing an eye for introducing photosensitizer, wherein channels 18 are created in the cornea by laser radiation 26 focused on and in the cornea, which extend from the surface 14a of the cornea into the interior the cornea extend. In this method, all the features and properties of the channels 18 described above can be used.

10

eye

M

Midpoint (out of 10)

A

eye axis

P

program

C

circumferentially

O

opening

12

eye tissue

14

Epithelium, 14a surface (from 14)

16

Cornea, 16a posterior surface (from 16)

18

channel

20

Source for laser radiation

22

computer

24

medium

26

laser radiation

28

arrows

30

limbo

Claims (14)

1. An apparatus for preparing an eye (10) for applying a photosensibilisator into the eye's tissue (12), comprising:

   - a source (20) for laser radiation,

   - means (24) for guiding and focusing the laser radiation (26) in relation to the eye's tissue (12), further comprising

   - a computer (22) for controlling said means (24), wherein the computer (22) is programmed to control the laser ration (26) such that the laser radiation generates in the eye's tissue (12) at least one channel (18) extending to the inner of the eye's tissue and generates one or more orifices (O) in the surface (14a) of the eye's tissue,
   characterized in that the computer is programmed to control said means (24) such that the one or more channels (18) are communicating with one or more orifices (O) in the surface (14a) of the eye's tissue.
2. The apparatus according to claim 1, characterized in that the one or more channels (18) extend a substantially transverse to the axis (A) of the eye.
3. The apparatus according to claim 1 or 2, characterized in that the computer (22) is programmed to control said means (24) such that the one or more channels (18) are applied into the eye's tissue (12) along lines extending substantially radially (R).
4. The apparatus according to any one of claims 1, 2 or 3, characterized in that the one or more channels (18) penetrate substantially the entire radial surface of the cornea (16) while having a substantially uniform channel density.
5. The apparatus according to any one of the preceding claims, characterized in that at least a part of the channels extends spirally.
6. The apparatus according to any one of the preceding claims, characterized in that the one or more channels (18) are generated at least partially by cavitation bubbles generated by the laser radiation, wherein the cavitation bubbles partially do not transit continually into one another, wherein the distance between neighboring cavitation bubbles is in the range from 1 to 50 µm, preferably in the range from 5 to 30 µm and particularly preferable in the range of 10 to 20 µm.
7. The apparatus according to any one of the preceding claims, characterized in that at least a part of the channels extends at least partially axially and/or at least partially curved.
8. The apparatus according to claim 1, characterized in that the computer (22) is programmed so as to control said means (24) such that channels (18) are applied into the eye's tissue (12), the density of which varies depending on the site in the eye's tissue.
9. The apparatus according to any one of the preceding claims, characterized in that the computer (22) is programmed to control said means (24) such that channels (18) are applied into eye's tissue (12), the depth and/or the section of which varies depending on the site in the eye's tissue.
10. The apparatus according to any one of the preceding claims, characterized in that the computer (22) is programmed to control said means (24) such that channels (18) are applied into the eye's tissue (12), wherein different channels have different sections.
11. The apparatus according to any one of the preceding claims, characterized in that the source (20) for laser radiation is one of a femtosecond laser, a nanosecond laser or a picosecond laser.
12. The apparatus according to any one of the preceding claims, characterized in that the computer is programmed to control said means (24) such that channels (18', 18") are generated into the eye's tissue for therapy of astigmatism, which channels approximately take the form of sectors.
13. The apparatus according to any one of the preceding claims, characterized in that the computer (22) is programmed to control said means (24) so as to generate one or more channels (18'") extending at least approximately annularly.
14. The apparatus according to any one of the preceding claims, characterized in that the computer (22) is programmed to control said means (24) such that channels (18a, 18b, 18c) are generated into the eye's tissue (12), which channels extend in different depths in the eye's tissue.

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